[Early detection of WHIM symdrome. A case report]. / Identificación temprana de síndrome de WHIM. Informe de un caso.

BACKGROUND: WHIM syndrome corresponds to an inborn error of innate and intrinsic immunity, characterized by: warts (Warts), Hypogammaglobulinemia, Infections and Myelocathexis, for its acronym in English. CASE REPORT: 4-year-old male, with severe neutropenia and B-cell lymphopenia from birth, without severe infections or warts; the panel genetic sequencing study of primary immunodeficiencies with the CXCR4 c.1000C>T (p.Arg334*) variant, which is associated with WHIM syndrome. CONCLUSIONS: The diagnosis of severe neutropenia from birth should include the search for inborn errors of immunity, through genetic sequencing studies, especially in asymptomatic or oligosymptomatic patients.

ANTECEDENTES: El síndrome WHIM corresponde a un error innato de la inmunidad innata e intrínseca, caracterizada por verrugas (Warts), hipogammaglobulinemia, infecciones y mielocatexis, por sus siglas en inglés. REPORTE DE CASO: Paciente masculino de 4 años, con neutropenia severa y linfopenia de células B desde el nacimiento, sin infecciones severas ni verrugas. El estudio de secuenciación genética informó la variante CXCR4 c.1000C>T (p.Arg334*), relacionada con el síndrome de WHIM. CONCLUSIÓN: El diagnóstico de neutropenia severa desde el nacimiento debe incluir la búsqueda de errores innatos de la inmunidad, mediante estudios de secuenciación genética, especialmente en pacientes asintomáticos u oligosintomáticos.

Amelanotic acral melanoma misdiagnosed as verruca plantaris.

We report a case of amelanotic acral melanoma in a 42-year-old Chinese woman. Ten months previously the patient found a 2-cm asymmetric erythematous macular plaque on her left sole. The lesion was diagnosed as verruca plantaris by every physician the patient consulted. One month ago, an enlarged lymph node was detected in the left groin, which biopsy reported as metastatic melanoma. Dermoscopy suggested verruca plantaris, and positron emission tomography (PET) revealed increased glucose metabolism in the macular plaque. Finally, biopsy of the plaque revealed amelanotic melanoma. Misdiagnosis and diagnostic delay are usually associated with poorer patient outcomes. Awareness of atypical presentations of acral melanoma is thus important for decreasing misdiagnosis rates and improving patient outcomes.

Amelanotic acral melanoma misdiagnosed as verruca plantaris

Abstract: We report a case of amelanotic acral melanoma in a 42-year-old Chinese woman. Ten months previously the patient found a 2-cm asymmetric erythematous macular plaque on her left sole. The lesion was diagnosed as verruca plantaris by every physician the patient consulted. One month ago, an enlarged lymph node was detected in the left groin, which biopsy reported as metastatic melanoma. Dermoscopy suggested verruca plantaris, and positron emission tomography (PET) revealed increased glucose metabolism in the macular plaque. Finally, biopsy of the plaque revealed amelanotic melanoma. Misdiagnosis and diagnostic delay are usually associated with poorer patient outcomes. Awareness of atypical presentations of acral melanoma is thus important for decreasing misdiagnosis rates and improving patient outcomes.

[Late diagnosis of WHIM sydrome]. / Diagnóstico tardío de síndrome WHIM.

WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.

Diagnóstico tardío de síndrome WHIM / Late diagnosis of WHIM sydrome

El síndrome WHIM es una inmunodeficiencia primaria de herencia autosómica dominante, debida a mutaciones en el gen CXCR4, que se caracteriza por verrugas cutáneo-mucosas, hipogammaglobulinemia, infecciones bacterianas recurrentes y mielocatesis. El tratamiento se basa en el uso de antibióticos profilácticos, gammaglobulina en dosis sustitutiva y factores estimulantes de colonias de granulocitos o de granulocitos y macrófagos, en forma crónica. Presentamos el caso de una mujer de 21 años que comenzó a los 10 meses de edad con leucopenia y al siguiente año múltiples infecciones con hipogammaglobulinemia requiriendo gammaglobulina endovenosa durante los episodios. Evolucionó con neutropenia crónica. Una punción aspiración de médula ósea mostró la serie mieloide aumentada con ligero predominio de elementos inmaduros. El cuadro fue interpretado como inmunodeficiencia común variable debido a la asociación de múltiples cuadros infecciosos, niveles disminuidos de IgG, IgM e IgA y linfopenia con disminución de linfocitos B de memoria, por lo que comenzó tratamiento sustitutivo con gammaglobulina endovenosa más antibióticos profilácticos. A los 20 años se registraron pequeñas verrugas en manos que progresaron hacia antebrazos, abdomen, cara y rodillas. Se realizaron estudios moleculares para la búsqueda de mutaciones en el gen CXCR4 donde se detectó la mutación p.Arg334STOP en estado heterocigota confirmando el diagnóstico de síndrome WHIM, que es una inmunodeficiencia infrecuente y de difícil diagnóstico.

WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.

Assessment of the carcinogenic potential of high intense-sweeteners through the test for detection of epithelial tumor clones (warts) in Drosophila melanogaster.

High intensity-sweeteners (HIS) are natural or synthetic substances, sweeter than sugar, providing sweetness without calories. Sweeteners are mainly used as an aid in losing weight, preventing obesity and controlling blood sugar levels for diabetics. The objective of this study was to evaluate the carcinogenic potential of the sweeteners aspartame, sucralose, sodium saccharin and steviol glycoside, using the test for detection of epithelial tumor clones in Drosophila melanogaster. Larvae of 72 ± 4h, obtained from wts/TM3 female mated with mwh/mwh males, were treated for approximately 48h with different concentrations of aspartame (0.85, 1.7, 3.4, 6.8 or 13.6 mM ); sucralose (0.5, 1.25, 2.5, 5.0 or 10 mM); sodium saccharin (25; 50; 100; 200 or 400 mM) and steviol glycoside (2.5; 5.0; 10; 20 or 40 mM). Water (Reverse Osmosis) and doxorubicin (DXR 0.4 mM) were used as negative and positive controls, respectively. No statistically significant differences were observed (p > 0.05) in tumor frequencies in individuals treated with all concentrations of these sweeteners when compared to negative control. It was therefore concluded that, in these experimental conditions, aspartame, sucralose, sodium saccharin and steviol glycoside have no carcinogenic effect in D. melanogaster.

Melanonychia induced by topical treatment of periungual warts with 5-fluorouracil.

Periungal and subungual warts are benign epidermal neoplasms caused by human papillomaviruses. They represent a challenge for management because of resistance to treatment. 5-flourouracil is an antimetabolite that interferes with DNA synthesis and inhibits RNA formation. We present a 32-year-old female with subungual and periungual warts of the fingers of both hands and first right toe. She was treated with 5-fluorouracil twice daily under occlusion plus 20 percent urea. After a month she presented with grayish transverse melanonychia along and parallel to the lunula with some maceration of the periungal folds. Nail pigmentation may be a consequence of dermal deposition by systemic drugs and less frequently by topical drugs. In this case melanonychia was induced by the topical application of 5-fluorouracil. The brown-grayish pigmentation, with parallel involvement of the lunula of all the nails treated, presented like that induced by systemically administered cytotoxic drugs.

Recognizing and treating anal cancer: training medical students and physicians in Puerto Rico.

OBJECTIVE: This training activity aimed at increasing the knowledge of anal cancer screening, diagnostic and treatment options in medical students and physicians, to determine the interest of these individuals in receiving training in the diagnosis and treatment of anal cancer, and to explore any previous training and/or experience with both anal cancer and clinical trials that these individuals might have. METHODS: An educational activity (1.5 contact hours) was attended by a group of medical students, residents and several faculty members, all from the Medical Sciences Campus of the University of Puerto Rico (n = 50). A demographic survey and a 6-item pre- and post-test on anal cancer were given to assess knowledge change. RESULTS: Thirty-four participants (68%) answered the survey. Mean age was 29.6 +/- 6.6 years; 78.8% had not received training in anal cancer screening, 93.9% reported being interested in receiving anal cancer training, and 75.8% expressed an interest in leading or conducting a clinical trial. A significant increase in the test scores was observed after the educational activity (pre-test: 3.4 +/- 1.2; post-test: 4.7 +/- 0.71). Three of the items showed an increase in knowledge by the time the post-test was taken. The first of these items assessed the participants' knowledge regarding the existence of any guidelines for the screening/treatment of patients with human papillomavirus (HPV)-related anal disease. The second of these items attempted to determine whether the participants recognized that anal intraepithelial neoplasia (AIN) 2 is considered to be a high-grade neoplasia. The last of the 3 items was aimed at ascertaining whether or not the participants were aware that warty growths in the anus are not necessarily a manifestation of high-grade AIN. CONCLUSION: This educational activity increased the participants' knowledge of anal cancer and revealed, as well, that most of the participants were interested in future training and in collaborating in a clinical trial. Training physicians from Puerto Rico on anal cancer clinical trials is essential to encourage recruitment of Hispanic patients in these studies now that the guidelines in anal cancer screening and treatment are on their way to be defined.

Tetralogy of fallot is an uncommon manifestation of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder. We report three patients with WHIM syndrome who are affected by Tetralogy of Fallot (TOF). This observation suggests a possible increased risk of TOF in WHIM syndrome and that birth presentation of TOF and neutropenia should lead to suspect WHIM syndrome.

Verruga umbilical / Umbilical wart

Las verrugas vulgares son proliferaciones epiteliales benignas, causadas por la infección del virus papiloma humano. Suelen afectar a niños y adolescentes comprometiendo frecuentemente manos y rodillas. Existen múltiples tratamientos pero ninguno infalible, y si bien se preconiza la conducta expectante, existen casos en los que se debe realizar tratamiento. Presentamos el caso de un escolar de sexo masculino con verruga umbilical, una localización infrecuente, tratada exitosamente con electrocoagulación.

Common warts are benign epithelial growths caused by infection with human papillomavirus. They usually affect children and adolescents often compromising hands and knees. There are many treatments but none infallible, and while it is recommended an expectant behaviour, there are cases in which treatment should be performed. We report the case of a 12 year old white male with an umbilical wart, an unusual localization, treated successfully with electrocoagulation.

Clinical and epidemiological profile of sexually transmitted diseases in children attending a referral center in the city of Manaus, Amazonas, Brazil.

BACKGROUND: Sexually transmitted diseases in children remain a public health concern that is relatively ignored. Further data are required on the management of these diseases and their association with child sexual abuse. OBJECTIVES: To describe the clinical and epidemiological profile of sexually transmitted diseases in children receiving care at a referral center in the city of Manaus, Amazonas, Brazil. METHODS: A descriptive, exploratory study was conducted to evaluate the clinical, epidemiological and laboratory characteristics of the sexually transmitted diseases (STD) found in children who received care at this clinic between January 2003 and December 2007. RESULTS: A total of 182 children with STDs were included in the study. The majority were female (65.4%), dark-skinned and with a mean age of 8.5 years. Furthermore, 89% were from the city of Manaus and their parents were usually responsible for having brought them to the clinic. Genital warts constituted the principal diagnosis in children of both sexes and 90.1% of the children had only one STD. CONCLUSIONS: The frequencies and clinical characteristics of the STDs in the children in this study were similar to data reported in the literature. Although the signs and symptoms of the STDs found in these children do not, in themselves, constitute reliable parameters by which to confirm abuse, professionals should always be alert to this possibility, since these diseases may represent a sign of sexual offenses that may be dissimulated and repetitive.

Perfil clínico-epidemiológico das doenças sexualmente transmissíveis em crianças atendidas em um centro de referência na cidade de Manaus, Amazonas, Brasil / Clinical and epidemiological profile of sexually transmitted diseases in children attending a referral center in the city of Manaus, Amazonas, Brazil

FUNDAMENTOS: Doenças Sexualmente Transmissíveis em crianças permanecem um problema de saúde pública pouco estudado, sendo ainda necessários esclarecimentos sobre seu manejo e a relação destas com o abuso sexual infantil. OBJETIVOS: Descrever o perfil clínico-epidemiológico das Doenças Sexualmente Transmissíveis em crianças atendidas em centro de referência na cidade de Manaus. MÉTODOS: Realizou-se estudo descritivo exploratório para verificar características clínicas, epidemiológicas e laboratoriais das Doenças Sexualmente Transmissíveis em crianças atendidas durante o período de janeiro/2003 a dezembro/2007. RESULTADOS: Foram incluídas no estudo 182 crianças que apresentavam DST. A maioria era do sexo feminino (65,4 por cento) e de cor parda; a média de idade foi de 8,5 anos; 89 por cento eram procedentes da cidade de Manaus; os pais foram os principais acompanhantes na consulta; verruga genital foi o principal diagnóstico em ambos os sexos; e, 90,1 por cento apresentavam apenas uma DST. CONCLUSÃO: As frequências e características clínicas das DST nas crianças do estudo não diferiram do encontrado na literatura. Embora, com base em sinais e sintomas referentes tão somente às DST nas crianças, não se tenham parâmetros fidedignos de confirmação de abuso, deve-se sempre estar alerta para esta possibilidade, visto que estas doenças podem ser sinalizadoras de ofensas sexuais, por vezes, dissimuladas e repetidas.

BACKGROUND: Sexually transmitted diseases in children remain a public health concern that is relatively ignored. Further data are required on the management of these diseases and their association with child sexual abuse. OBJECTIVES: To describe the clinical and epidemiological profile of sexually transmitted diseases in children receiving care at a referral center in the city of Manaus, Amazonas, Brazil. METHODS: A descriptive, exploratory study was conducted to evaluate the clinical, epidemiological and laboratory characteristics of the sexually transmitted diseases (STD) found in children who received care at this clinic between January 2003 and December 2007. RESULTS: A total of 182 children with STDs were included in the study. The majority were female (65.4 percent), dark-skinned and with a mean age of 8.5 years. Furthermore, 89 percent were from the city of Manaus and their parents were usually responsible for having brought them to the clinic. Genital warts constituted the principal diagnosis in children of both sexes and 90.1 percent of the children had only one STD. CONCLUSIONS: The frequencies and clinical characteristics of the STDs in the children in this study were similar to data reported in the literature. Although the signs and symptoms of the STDs found in these children do not, in themselves, constitute reliable parameters by which to confirm abuse, professionals should always be alert to this possibility, since these diseases may represent a sign of sexual offenses that may be dissimulated and repetitive.

Diseases mimicking onychomycosis.

The diagnosis of onychodystrophy has increased in dermatology consultation. This could be due to its esthetic effect, pain or disability, physician awareness for detecting the disease in the context of dermatologic or systemic diseases, or a greater incidence. One of the first differential diagnoses that should be considered when an onychodystrophic nail is observed is onychomycosis, which is the cause in 50% of cases.

[Diagnosis and treatment of human papilloma virus]. / Diagnóstico y terapia del virus papiloma humano.

The identification and treatment of human papillomavirus (HPV) infections and HPV-associated neoplasm are complex. Difficulties in diagnosis and treatment of HPV-associated diseases arise from inabilities to detect HPV efficiently, the lack of specific antiviral drugs active against HPV and the high rates of recurrence and persistence of HPV infections after treatment. We present a review of therapies for HPV infections.

Diagnóstico y terapia del virus papiloma humano / Diagnosis and treatment of human papilloma virus

Tanto el diagnóstico como el tratamiento de la infección producida por el virus papiloma humano y el cáncer asociado a este virus, nos plantean uno de los mayores desafíos en la última década. Las principales dificultades radican en la identificación del genotipo viral, la ausencia de una terapia antiviral efectiva y las altas tasas de recurrencia y persistencia a pesar de la terapia empleada. Se presenta un resumen de la terapia disponible en la actualidad.

The identification and treatment of human papillomavirus (HPV) infections and HPV-associated neoplasm are complex. Difficulties in diagnosis and treatment of HPV-associated diseases arise from inabilities to detect HPV efficiently, the lack of specific antiviral drugs active against HPV and the high rates of recurrence and persistence of HPV infections after treatment. We present a review of therapies for HPV infections.